You are on page 1of 18

Hindawi Publishing Corporation

Dermatology Research and Practice


Volume 2012, Article ID 198789, 18 pages
doi:10.1155/2012/198789

Review Article
The Infant Skin Barrier: Can We Preserve, Protect,
and Enhance the Barrier?

Lorena S. Telofski,1 A. Peter Morello III,2


M. Catherine Mack Correa,1 and Georgios N. Stamatas3
1 JOHNSON & JOHNSON Consumer Companies, Inc., 199 Grandview Road, Skillman, NJ 08558, USA
2 Evidence
Scientific Solutions, 123 South Broad Street, Suite 1670, Philadelphia, PA 19109, USA
3 JOHNSON & JOHNSON Santé Beauté France, 1 rue Camille Desmoulins, 92787 Issy-les-Moulineaux, France

Correspondence should be addressed to Lorena S. Telofski, ltelofs@its.jnj.com

Received 20 April 2012; Accepted 15 June 2012

Academic Editor: Alex Zvulunov

Copyright © 2012 Lorena S. Telofski et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

Infant skin is different from adult in structure, function, and composition. Despite these differences, the skin barrier is competent
at birth in healthy, full-term neonates. The primary focus of this paper is on the developing skin barrier in healthy, full-term
neonates and infants. Additionally, a brief discussion of the properties of the skin barrier in premature neonates and infants with
abnormal skin conditions (i.e., atopic dermatitis and eczema) is included. As infant skin continues to mature through the first
years of life, it is important that skin care products (e.g., cleansers and emollients) are formulated appropriately. Ideally, products
that are used on infants should not interfere with skin surface pH or perturb the skin barrier. For cleansers, this can be achieved
by choosing the right type of surfactant, by blending surfactants, or by blending hydrophobically-modified polymers (HMPs)
with surfactants to increase product mildness. Similarly, choosing the right type of oil for emollients is important. Unlike some
vegetable oils, mineral oil is more stable and is not subject to oxidation and hydrolysis. Although emollients can improve the skin
barrier, more studies are needed to determine the potential long-term benefits of using emollients on healthy, full-term neonates
and infants.

1. Introduction susceptible to infection [3]. During the late fetal period (20
weeks to birth), skin becomes functional and develops a
Skin barrier function resides primarily within the stratum protective barrier [8]. Although full-term infants are born
corneum (SC), the top layer of the epidermis. Although the with a competent skin barrier [9, 10], their skin is still
SC is only 7–35 μm thick [1, 2], it plays a vital role in forming developing through the first year of life [2, 11]. During
a protective barrier and helps to prevent percutaneous entry the postnatal period, even the composition of commensal
of harmful pathogens into the body [3, 4]. In addition to bacteria residing on the skin surface differs from that of
serving as a physical barrier, the SC has other important adults and continues to evolve over the first year of life [12].
functions, including engaging in thermoregulation, gas Given that skin continues to develop through the first
exchange, and maintenance of proper hydration. The SC also year of life, the use of appropriate, evidence-based skin care
serves important functions in innate immunity [5] and its practices is important. Maintaining skin barrier function
slightly acidic pH [6] provides additional protection against is critical to preventing organ dehydration [13]. The SC
pathogens. water content is involved in maintaining SC structural
Maintenance of the skin barrier is essential for survival integrity and functionality [14]. It is generally accepted that
[1]. This is especially true for neonates and infants because recommendations for infant skin care regimens should be
their skin differs from mature adult skin in structure, evidence-based [15]. Although several studies have evaluated
function, and composition [1, 2, 7] and is particularly nonprescription emollient strategies to improve barrier
2 Dermatology Research and Practice

function [16, 17] or improve fluid and electrolyte balance structural and morphologic differences between infant and
[18] in neonates, infants, or children with compromised skin, adult skin [2]. These differences may lead to observable
limited information is available on skin care regimens that functional differences between infant and adult skin [11].
enable maintenance or enhancement of skin barrier integrity Table 1 contains an overview of the major similarities and
in normal neonatal or infant skin [19, 20]. differences between infant and adult skin.
Skin cleansing and emollient use are two simple strategies The water-handling properties of infant skin are unique
that can help keep skin healthy. Proper skin cleansing helps and distinct from adult skin. Figure 1 shows a schematic of
keep infant skin free of unwanted irritants, including saliva, infant and adult SC hydration and their respective water-
nasal secretions, urine, feces, fecal enzymes, dirt, and micro- holding properties. Neonatal skin after birth is considerably
bial pathogens. Exposure to such factors for long periods, drier compared with that of adults [31, 32]. However, during
especially in the diaper region, can lead to discomfort, the first month of life, the difference in SC hydration between
irritation, infection, and skin barrier breakdown. In many infants and adults is reversed [32, 33], leading to increased
cases, water alone is not sufficient to cleanse skin during skin hydration in older infants (aged 3–24 months) relative
bathing [21]. Epidemiologic studies and anecdotal reports to adult skin [11, 34]. As skin becomes more hydrated, the
have even suggested a possible link between household use SC that is initially rough smoothens [32].
of hard water and atopic eczema in children [22, 23], though In addition to undergoing structural and functional
a causal relationship has not been shown [24, 25]. changes, the composition of the cutaneous microflora
In addition to using cleansers during bathing, emollient evolves over the first year of life [12]. Although adult skin
use during or after bathing also may have benefits [16– is colonized mostly by the phyla Proteobacteria, Actinobac-
20, 26–29]. Emollients decrease transepidermal water loss teria, and Firmicutes, the order of predominance changes in
(TEWL) [16, 17, 26], improve skin condition [17, 26], and infant skin to Firmicutes (predominantly Staphylococci), fol-
may even lead to reduced mortality in extremely premature lowed by Actinobacteria, Proteobacteria, and Bacteroidetes
infants [28]. In adults, 7 weeks of emollient use led to [12]. Although the implications of these findings are not yet
improvement in skin barrier function [27]. known, early microbial colonization is expected to influence
In this paper, we discuss the unique structure, function, the development of immune function in skin. It also will
and composition of infant skin, the importance of maintain- be important to characterize the further evolution of the
ing skin barrier integrity, and best practices for maintaining human skin microbiome during the first few years of life
or improving infant epidermal barrier function, including to determine if commensal bacteria play a role in the
use of appropriately formulated cleansers and emollients. We maintenance of skin barrier function beyond serving as
also discuss various neonatal and infant skin care guidelines sentinels of innate immune defense [35].
from around the world and some controversies surrounding
these guidelines. Finally, we will explore the idea that the
onset of emollient use from birth may play a role in 3. The Skin Barrier Is Competent at Birth in
preserving and protecting the infant skin barrier later in life. Healthy, Full-Term Neonates
After birth, skin barrier function is influenced by the shift
2. Infant Skin: Structure, Function, from an aqueous, warm environment in utero to a cooler,
and Composition arid, and more variable extrauterine world [11, 36]. Skin
development is contingent on gestational age. As gestation
Infant skin is different from adult skin: it undergoes a increases, the thickness and the number of cell layers in
maturation process through at least the first year of life the epidermis increase [9]. Morphologic changes also occur,
[2, 7, 11]. Several groups have measured or compared the including the formation of an increasingly undulated der-
epidermis of infants and adults [1, 2, 9, 30]. In one study, moepidermal junction [9]. Histologically, a well-developed
the epidermis of full-term neonates at birth was found to epidermis emerges at 34 weeks of gestation [9], though
have 4.3 ± 0.7 cell layers that were vertically stacked from the the period required for complete SC maturation has been
basal layer to the stratum granulosum (excluding the SC), reported to vary between 30 and 37 weeks [10].
whereas the epidermis of preterm neonates at birth had only Although infant skin is different from adult skin [2, 11],
2.9 ± 0.5 cell layers [9]. In their review of the literature, studies assessing the histologic and biophysical properties of
Chiou and Blume-Peytavi [1] reported that SC thickness the SC have demonstrated that the skin barrier is competent
ranged from 5.6 μm to 35.4 μm for infants and 15.2 μm to at birth in healthy, full-term neonates to prevent organ
35.4 μm for adults. Our group found that the suprapapillary dehydration [9, 10, 13]. The barrier properties of the skin
epidermis and the SC had respective thicknesses that were on depend greatly on the thickness and integrity of the SC [8, 9].
average 20% and 30% thinner in infants than in adults [2]. As would be expected, preterm infants have a skin barrier
On the lower thigh area, infant SC was determined to be 7.3 that is underdeveloped compared with full-term neonates
± 1.1 μm, whereas adult SC on the same region was 10.5 ± [9]. In one study [9], the epidermal thickness of full-term
2.1 μm [2]. neonates at birth was 43 ± 7 μm versus 31 ± 7 μm for preterm
At birth, full-term neonates have competent barrier infants (24–30 weeks of gestation).
function [10, 13] and an epidermis that appears to be In addition to SC thickness, other parameters can be used
fully differentiated [9], but closer examination reveals subtle to assess barrier function, including skin water-handling
Dermatology Research and Practice 3

Table 1: Infant and adult skin: similarities and differences.


Structural differences Infant skin Adult skin Reference
Epidermis
Corneocytes Smaller Larger [2]
Granular cells Smaller Larger [2]
Stratum corneum and epidermis Thinner Thicker [1, 2]
Microrelief lines More dense Less dense [2]
Depth of surface glyphics Similar to adult — [2]
Facultative pigmentation (melanin) Less More [142, 143]
Dermis
Dermal papillae (density, size, and morphology) More homogeneous Less homogeneous [2]
Distinct papillary-to-reticular dermis transition Absent Present [2]
Compositional differences
Epidermis
Natural moisturizing factor concentration Lower Higher [11]
pH Higher (newborn only) Lower [6, 32, 34]
Sebum Lower (7–12 month-old infant) Higher [144]
Stratum corneum water content Higher Lower [11]
Dermis
Collagen fiber density Lower Higher (young adult) [2, 145]
Functional differences
Rate of water absorption Higher Lower [11]
Rate of water desorption Higher Lower [11]
Skin barrier function Competent Competent [9, 10]
Transepidermal water loss Higher Lower [11]

(a) (b)

Figure 1: Infant and adult skin: stratum corneum (SC) hydration and water transport properties. The SC of infant skin (a) and adult skin
(b) is hydrated (small blue spheres) under normal conditions. Infant SC is more hydrated but also loses water at higher rates than adult SC
[11].
4 Dermatology Research and Practice

properties [11, 34]. Water barrier function and skin hydra- participant age (infant versus child), gender mismatch, body
tion status are interdependent factors, the former of which location (volar forearm versus buttock), or instrumentation.
is influenced largely by the organization and composition It should be noted that adult skin surface pH also has
of the intercellular lipid matrix [37], natural moisturizing been shown to vary by a wide margin [49]. Taken together,
factor [38], and the permeation path length through the SC published data indicate that skin surface pH is close to
[39]. Skin water content also influences skin barrier function neutral at birth and becomes more acidic over the first few
by regulating the activity of hydrolytic enzymes that are days of life. Within a matter of weeks, skin surface pH is
involved in SC maturation and corneocyte desquamation similar to levels observed in adults. However, consensus has
[40]. not been reached on the duration of this transition period.
Researchers can assess the skin’s capacity to absorb
and retain water with sorption-desorption tests that use
electrical measurements (e.g., skin surface conductance or 4. Maintenance of Skin Barrier Integrity
capacitance) before and after topical application of water on Is Essential to Overall Health and Wellness
the skin surface [1, 41]. Water barrier function, which affects
Skin barrier function is essential for survival [1] and is
rates of water absorption and desorption, is localized within
critical to preventing percutaneous entry of bacteria and
the SC [42] and has been shown to vary between infants
other pathogens into neonatal skin [50]. If the skin barrier
and adults [11, 31]. In addition, water content within the SC
is disturbed, bacteria or bacterial factors will have access
can have a profound effect on skin surface morphology [43],
to living epidermal keratinocytes and can induce defensive
desquamation [44], and epidermal expression of keratins
immune responses [4]. Keratinocytes produce antimicrobial
and cornified envelope proteins [45].
peptides (AMPs), including the cathelicidin-derived peptide
Newborn skin has been reported to have lower skin
LL-37 and human β-defensins 1-3 [4]. In the absence of
surface hydration and increased water loss compared with
AMPs, pathogenic microorganisms can invade the surface of
skin from 1- to 6-month-old infants or adults [31]. Our
skin, leading to infection or an imbalance of commensal flora
group also found that infant skin (3–12 months) on the
versus pathogenic bacteria. For example, patients suffering
upper ventral arm and lower dorsal arm gained and lost
from burns, chronic wounds, surgery, or injuries that are
water at significantly faster rates than the same regions on
associated with skin barrier dysfunction are more susceptible
adult skin [11]. Skin surface hydration on the upper ventral
to infections caused by Pseudomonas aeruginosa [4], yet this
arm and lower dorsal arm was greater in infants than adults.
opportunistic pathogen rarely causes infections on healthy
The distribution of water in the SC varied between infants
human skin [4].
and adults based on water concentration profiles calculated
using confocal Raman microspectroscopy. Infants had more
water on the skin surface, more water within the SC, and 5. Abnormal Infant Skin Conditions and
more water distributed throughout the first 26 μm below Barrier Integrity
the skin surface. Infant SC also had a steeper water gradient
compared with adult skin. 5.1. Atopic Dermatitis (AD). During childhood, skin disor-
TEWL is a noninvasive method that can be used to ders that are characterized by skin barrier dysfunction are
monitor changes in SC barrier function [46]; it also enables common. Compromised skin barrier integrity is thought to
dynamic measurement of water loss [11]. High basal TEWL be critical to the early onset and severity of AD, which is
is suggestive of incomplete skin barrier function and is often accompanied by dry, scaly skin. AD is an inflammatory
indirectly proportional to the integrity of water barrier skin condition that occurs in 15–20% of children [51, 52].
function. This method has been used to confirm that Alterations in skin barrier properties that are observed in
epidermal permeability barrier function is developed fully AD include increased TEWL [53], changes in skin surface
at birth in full-term neonates [6, 10]. In older infants (3– pH [54], increased skin permeability [55], increased bacterial
12 months) our group found that TEWL was significantly colonization [56], alterations in AMP expression [57],
higher compared with adult skin (P < .0005; 3–6 and 7–12 and compromised skin permeability barrier integrity [58].
months old versus adult) [11]. Once the skin barrier is compromised, allergens, irritants,
Formation of an acidic SC is essential for epidermal and other unwanted agents can penetrate skin, leading to
barrier maturation and repair processes [10]. Many factors aggravation of symptoms associated with AD.
contribute to formation of the acid mantle, including sebum There are several guidelines that discuss how caregivers
secretion, sweat (lactic acid), amino acids and amino acid can manage and treat AD [59, 60]. Recommendations to
derivatives (urocanic acid and pyrrolidone carboxylic acid), relieve AD include using warm water in lieu of hot water,
and exocytosis of lamellar body contents at the stratum taking short baths (5–10 minutes), and using a liquid
granulosum/stratum compactum interface [47]. At birth, cleanser with emollient that does not compromise skin
full-term neonates have a skin surface pH that varies between barrier integrity, followed by gentle dry patting with a soft
6.34 and 7.5 [6, 48]. Within the first 2 weeks of life, skin towel and immediate application of a skin emollient [29, 61].
surface pH falls to approximately 5 [3, 48], which is similar to The Royal College of Paediatrics and Child Health
the skin surface pH that has been observed during adulthood (RCPCH) presented a tiered approach to the management
(pH range: 4.0 to 6.7) [6, 49]. Discrepancies in skin surface of mild, moderate, and severe atopic eczema [62]. In all
pH between studies could be the result of differences in three cases, the RCPCH noted that initial treatment should
Dermatology Research and Practice 5

focus on repairing the skin barrier through the use of that have a demonstrated safety/tolerance profile [74].
emollients for moisturizing, washing, and bathing. Depend- In contrast, the National Institute for Clinical Excellence
ing on severity, emollient use can be supplemented with (NICE) clinical guideline 37 on postnatal care states the
topical corticosteroids. In cases of moderate atopic eczema, following [75]: “Parents should be advised that cleansing
bandages and topical calcineurin inhibitors (second-line agents should not be added to a baby’s bath water nor should
treatment) can be used to supplement emollient use. During lotions or medicated wipes be used. The only cleansing agent
severe atopic eczema, emollient use can be supplemented suggested, where it is needed, is a mild non-perfumed soap.”
with phototherapy and systemic therapy. Despite these recommendations, there is limited evidence to
support the NICE position on infant cleansing [29]. Water
is insufficient for removal of all oil-soluble skin surface
5.2. Irritant Diaper Dermatitis. Irritant diaper dermatitis is
impurities [76, 77] and has poor pH-buffering action [78].
a complex skin condition that is characterized by compro-
Depending on bathing frequency and quality of water used,
mised epidermal barrier function occurring on the buttocks,
washing with water alone can have a drying effect on infant
perianal region, inner thighs, and abdomen. Skin occlusion,
skin [29], which may lead to impairment of infant skin
friction, lipolytic and proteolytic activity of fecal enzymes,
condition. Although soap is an effective skin cleanser, it can
increased skin surface pH, and prolonged exposure to urine
disrupt skin surface pH, alter skin lipids, and cause dryness
are all contributing factors to the onset of irritant diaper
and irritation [79–81], all of which may make soap less
dermatitis [63]. Greater than 50% of infants will have at least
preferable.
one episode of irritant diaper dermatitis during the diaper-
On 13 February 2007, a group of clinical experts
wearing phase [64]. Clinical presentation of irritant diaper
in pediatrics and dermatology formed the first European
dermatitis includes skin erythema [65], but severe cases may
Round Table meeting on “Best Practice for Infant Cleansing.”
lead to presentation of papules and edema [66].
The consensus panel recommended that caregivers use
Within the past 10 years, there have been several
liquid, pH-neutral, or mildly acidic cleansers over traditional
reviews discussing the etiology and management of irritant
alkaline soaps on neonates and infants [29]. In addition, the
diaper dermatitis [67–71]. Although use of appropriately
consensus panel made the following recommendations:
formulated cleansers and emollients can help maintain the
epidermal skin barrier in the diaper region, good hygiene (i) Liquid cleansers are preferable to water alone.
and adequate protection are necessary to prevent skin barrier
(ii) Liquid cleansers cleanse and hydrate skin better than
breakdown, rash, and infection.
water alone.
(iii) Liquid preparations, which often contain emollients,
6. Cleansing Is Vital to Maintaining Good are preferable to cleansing bars.
Health and Hygiene (iv) Liquid cleansers should contain adequate and appro-
6.1. Infant Skin Care Guidelines, Recommendations, and priate preservatives.
Review of the Literature. Keeping babies clean and good (v) An “ideal cleanser” is one that does not cause
skin hygiene are essential to overall health. Cleansing helps irritation, alterations to skin surface pH, or eye
keep skin free of unwanted substances, including irritants stinging.
(saliva, nasal secretions, urine, feces, and fecal enzymes), (vi) Skin care products should be selected on the basis of
dirt, and transient germs. Keeping hands clean, particularly evidence acquired in practical use conditions.
in the case of babies with their hand-to-mouth behaviors,
can help reduce or prevent oral transmission of microbial Although the consensus panel recommended using liq-
contaminants. Caregivers should give special attention to uid cleansers and believed that liquid cleansers have some
skin on the facial area, which may be irritated easily by milk, desirable properties, to our knowledge no peer-reviewed
food, and saliva. Skin folds and creases on the face also publications have summarized the results from randomized
should be kept clean. controlled trials comparing the tolerance or efficacy of liquid
Although the benefits of good hygiene are known, or rinse-off cleansers to traditional soaps or syndet bars. In
neonatal skin cleansing and the use of cleansers, soaps, or an open-label, controlled, randomized study, Gfatter et al.
other topicals during the bathing process is controversial. For compared the effects of washing infant skin with a liquid
most of the 20th century there were no formal guidelines detergent (pH 5.5), compact detergent (pH 5.5), or alkaline
on neonatal skin cleansing. In 1974, the American Academy soap (pH 9.5) with a control group washing with water alone
of Pediatrics recommended that caregivers cleanse neonatal after a single wash [79]. Their study was designed to assess
skin after the infant’s temperature stabilizes [72]. In 1978, the effect of skin care regimens on pH, fat content, and skin
Sweden and Great Britain proposed similar recommenda- hydration. Although all cleansing regimens tested (including
tions [73]. In 2007, the Second Edition of the Associa- the control) were shown to influence the parameters studied,
tion of Women’s Health, Obstetric, and Neonatal Nurses the soap bar had the largest influence on skin pH and fat
(AWHONN) Neonatal Skin Care Evidence-Based Clinical content, resulting in statistically higher pH (more alkaline)
Practice Guideline recommended that caregivers select mild and statistically greater loss of fat. The study by Gfatter et
cleansing bars or liquid cleansers that have a neutral pH al. concluded that the short-term effects from a single wash
(5.5 to 7.0) that are preservative-free or contain preservatives can disturb the skin acid mantle and its protective function,
6 Dermatology Research and Practice

which suggests the need to determine the long-term effects urine, fecal matter, and fecal enzymes with minimal effort
of cleansing products and other skin care regimens [81]. [66, 80, 81].
Given the lack of harmonization across infant skin Although most cleansers and soaps are suitable for adult
cleansing guidelines, bathing practices vary widely. Siegfried bathing, cleansers for neonatal or infant skin should be
and Shah surveyed skin care cleansing practices in 15 formulated specifically for that population and its special
neonatal nurseries from 12 hospitals in Missouri, Iowa, needs. An ideal infant cleanser should contain at least
Illinois, and California [82]. Of these nurseries, four were one “surface-active agent” (surfactant), a molecule with
defined as “low risk” and 11 were defined as “high risk.” Head both hydrophilic and oleophilic (lipophilic) properties that
nurses, nursery directors, or other healthcare professionals reduces the interfacial tension between oil and water. Sur-
were asked questions about bathing practices, cord care, factants enable formation of oil-in-water, water-in-oil, and
and general infant skin care. Bathing of full-term infants in more complex, multiphasic systems. By reducing interfacial
tension, cleansers help to emulsify oils and other skin surface
the low-risk nurseries occurred on the first day when the
impurities into water [77], making their removal easier
infant was stable or when the infant’s core temperature was
without requiring excessive friction or mechanical force
98.6◦ F. There was little variation in the cleansing products during bathing.
used during bathing. Nine of 15 nurseries used a mild baby Several classes of surfactants are used often in cleanser
cleanser. One nursery used more than one brand, and no formulations, including anionic surfactants such as sodium
information was given about the cleansing products used at lauryl sulfate (SLS) or sodium laureth sulfate (SLES),
the other five nurseries. nonionic surfactants (e.g., poloxamers), and amphoteric
Garcia Bartels et al. evaluated the effect of bathing with or surfactants (e.g., cocamidopropyl betaine). Foaming action
without a liquid cleanser on skin barrier function in healthy, and mildness are influenced by the charge of a surfactant’s
full-term neonates [19]. TEWL, SC hydration, skin surface hydrophilic head group and the formation of spherical
pH, and sebum were measured on the forehead, abdomen, structures (micelles) that enable solubilization of oils and
upper leg, and buttock on day 2, week 2, 4, and 8 of life. After lipids from the skin surface [21]. Although anionic and
8 weeks of life, skin surface pH was significantly lower in amphoteric surfactants facilitate foam formation (a desirable
neonates who were bathed with a liquid cleanser versus those aesthetic property for shampoo), they are usually less mild
who were bathed with water alone. Bathing with a liquid than nonionic surfactants such as polyethylene glycol (PEG)-
cleanser did not lead to significant differences in median 80 sorbitan laurate.
TEWL values or SC hydration on any of the tested body sites Surfactant selection represents a tradeoff between func-
versus those who were bathed with water alone. Moreover, tionality, aesthetics, and mildness. Due to their charge and
use of a liquid cleanser did not lead to statistically significant ability to form smaller micelles relative to other surfactants,
changes in sebum measurements. The use of a liquid cleanser some anionic surfactants can be disruptive and irritating to
was well tolerated in healthy, full-term neonates during the skin [21, 81]. For example, SLS is an effective emulsifying
first 8 weeks of life. The study by Garcia Bartels et al. did not and foaming agent, but in certain circumstances it may
cause irritation [81, 84]. In contrast, PEGylated nonionic
include premature neonates or infants with abnormal skin
surfactants (e.g., PEG-80 sorbitan laurate or polyethylene
conditions and it is not known if similar observations would
oxides) can lead to micelle stabilization, potentially increas-
be made in premature neonates or those with compromised
ing cleanser mildness [21]. Cleansers containing sulfated
skin. ethoxylated alcohols (e.g., SLES), surfactants that have large
In a randomized, investigator-blinded clinical study, head groups and have the ability to form larger micelles, may
Dizon et al. compared the effects of twice-daily washing with be formulated to have improved mildness compared with
water alone versus washing with water and a mild cleanser or those containing SLS [84, 85]. In 20 healthy adult volunteers,
water with a comparator cleanser for 2 weeks in 180 healthy patch testing revealed that SLES was milder and caused
infants [83]. After 2 weeks, cleansing with water alone led to significantly less damage to the epidermal barrier compared
a significant increase in erythema from baseline. In contrast, with SLS [84]. After 7 days, no significant irritation was
there was no change in skin erythema from baseline in the observed with SLES, even at the highest tested concentration
group that was cleansed with water and mild cleanser. (2.0%). Regeneration after skin irritation occurred much
faster with SLES compared with similar concentrations of
6.2. Formulation Considerations. Many traditional soaps SLS [84]. In 2010, the Cosmetic Ingredient Review (CIR)
contain detergents that are derived from saponification (e.g., panel concluded that SLES is safe as a cosmetic ingredient
the process of mixing a strongly alkaline solution with a fatty when used appropriately in products formulated to be
substance such as vegetable oil or tallow, leading to soap nonirritating [86].
formation) [76]. Alkaline soaps can increase skin surface Mild moisturizing cleansers are expected to provide
pH beyond what is considered an ideal range [76, 79]; cleansing benefits without negatively altering the hydration
they can also dissolve fat-soluble and water-soluble barrier and viscoelastic properties of skin [81]. Formulators can
components from the surface of skin [79]. Unlike traditional combine surfactants to create milder cleansers [21], which
soaps, many of which can be irritating, infant cleansers may be particularly ideal for individuals with AD [87].
should be mild to accommodate the maturing skin barrier. For example, liquid body cleansers that contain a blend
Infant cleansers should also wash away dirt, sebum, saliva, of anionic and amphoteric surfactants can be milder than
Dermatology Research and Practice 7

a liquid cleanser that contains an equal proportion of Bernhofer et al. demonstrated that IL-1α can be a
anionic surfactant alone. The blending of hydrophobically- useful predictor of skin mildness and irritation potential
modified polymers (HMPs) with surfactants also may lead [93]. Levels of subclinical irritation—even in the absence
to increased cleanser mildness [88]. HMPs can interact with of visible erythema—can be determined using a noninva-
and associate with the hydrophobic tails of other surfactants, sive epidermal tape-stripping technique and enzyme-linked
leading to self-assembly and the formation of larger surfac- immunosorbent assay [95, 96]. IL-1 receptor antagonist (IL-
tant/polymeric structures. The creation of micelles with a 1ra), IL-1α, and the ratio between these two molecules
larger hydrodynamic diameter has been shown to have lower are useful for assessing skin reactivity [95] and measuring
irritation potential and may ultimately allow for the creation skin inflammation [95, 97]. The IL-1ra/IL-1α ratio increases
of milder surfactant systems and better tolerated cleansers during infancy, irritant diaper dermatitis, heat rash, and
[88]. erythema [96]. By extension, the IL-1ra/IL-1α ratio also may
The properties of an ideal infant cleanser are summarized help predict the irritation potential of skin cleansers [93].
in Table 2. Traditional cleansers are formulated to have a pH It is anticipated that skin treated with a mild skin cleanser
that is similar to that of the skin surface. Liquid cleansers would have a lower IL-1ra/IL-1α ratio compared with skin
should be nonirritating and should enable maintenance of treated with a more irritating cleanser, possibly leading
normal skin surface pH [29]. If the pH of a cleanser is to a more normalized skin condition. Table 3 shows the
acidic but does not perturb skin surface pH, it may be proinflammatory activity of several commercially available
preferable to one that is pH neutral that causes a greater cleansing products whose irritation potential was assessed by
shift in skin surface pH. Solutions that are not pH neutral measuring IL-1α release using in vitro skin tissue equivalents
are not necessarily more irritating to skin. Moreover, it (EpiDerm, MatTek Corporation, Ashland, MA, USA). A mild
could be argued based on the weight of the evidence that baby cleanser and mild baby shampoo caused less IL-1α
alkaline cleansers would be least appropriate. Alkaline soap release compared with a commercial sensitive skin syndet
can disrupt skin surface pH [79], decrease SC thickness bar. Moreover, MTT cell proliferation (cell viability) assay
[89], decrease SC intracellular lipids [89], and lead to data revealed that there was more cell cytotoxicity associated
dryness and irritation [80, 81]. Buffer solutions with varying with the sensitive skin syndet bar. Although these data are
pH (4.0 to 10.5) were shown to be nonirritating to skin from in vitro skin equivalents, the mild baby cleanser and
irrespective of pH [90]. In addition, detergents buffered at mild baby shampoo would be expected to cause minimal
pH 3.5 or 7.0 caused similar levels of skin irritation [90]. release of IL-1α from infant skin, possibly leading to less skin
Although cleansers can alter skin surface pH, temporary pH irritation. Other methods for assessing cleanser mildness
fluctuations may be stabilized by the skin’s large buffering include measuring the percutaneous transit time, protein
capacity [90]. A cleanser’s effect on skin surface pH may solubilization, or collagen-swelling potential [98].
be more important than the pH of the formulation itself in
determining product mildness.
There are conflicting reports in the literature about 7. Emollients Can Improve Skin Barrier
the effect of cleansers on cutaneous commensal bacteria. Function in Healthy, Full-Term Neonates
Maintaining a skin surface pH between 4.0 and 4.5 facilitates
cutaneous commensal bacterial attachment to the surface of Dry, scaly skin is common in neonates [31] but can occur at
skin [49]. Larson and Dinulos hypothesized that inappro- any stage of development. Although many factors contribute
priately formulated soaps could alter the delicate balance to skin surface hydration, the environment (i.e., dry, cold
between cutaneous commensal and pathogenic bacteria [3]. weather or wind) can accelerate the loss of moisture from
da Cunha and Procianoy investigated the effect of using the SC. Emollients have been used for centuries to protect
a pH-neutral soap during bathing on cutaneous bacterial the integrity of the SC and to maintain skin barrier function
colonization in infants admitted to a neonatal intensive [99]. Appropriately formulated emollients can preserve,
care unit [91]. After 1 week, the use of a pH-neutral soap protect, and enhance the infant skin barrier by supplying
did not have an effect on cutaneous bacterial colonization the SC with water and lipids and by helping to inhibit water
compared with infants who were bathed with water alone. loss. Emollients also supply lipids to epidermal keratinocytes,
Given the importance of cutaneous commensal bacteria to where they can be transported through the cell membrane
innate immunity [92], the use of mild cleansers that do not and metabolized within the cell [100]. Keratinocytes can then
cause alterations in skin surface pH may be important for use lipids (including linoleic acid) as components to build a
normal skin maturation and innate immune function. functional epidermal barrier [101].
Several studies have shown that emollient use can
6.3. Noninvasive Approaches to Predict Skin Irritation Poten- improve skin barrier function [16, 17] or improve fluid and
tial. Interleukin-1α (IL-1α) and prostaglandin E2 mediate electrolyte balance [18] in preterm infants, but very few
inflammation in skin via cytokine-dependent and arachi- studies have investigated the use of emollients on healthy,
donic acid-dependent pathways, both of which play a role in full-term neonates [19, 20]. Garcia Bartels et al. investigated
the development of erythema and edema. Proinflammatory the effect of applying topical emollients on healthy, full-term
markers (including IL-1α) that are indicative of subclinical neonates after bathing with or without liquid cleanser on
inflammation (i.e., erythema) may be useful in predicting the skin barrier function during the first 8 weeks of life [19].
skin irritation potential of a skin cleansing product [93, 94]. After 8 weeks, median TEWL was significantly lower on the
8 Dermatology Research and Practice

Table 2: Ideal properties of appropriately formulated cleansers for neonates and infants.

Property Traditional cleanser Infant cleanser


Surfactant systems Amphoteric, anionic Amphoteric, nonionic, and ethoxylated anionic
Micelle diameter Smaller Larger
pH Slightly acidic to neutral pH pH should cause minimal changes to skin surface pH
Estimated IL-1ra/IL-1α ratio Larger Smaller
Preservative system Some claim preservative-free Product should be “microbiologically robust”
Lower concentration level; restrictions on specific fragrance
Fragrance (parfum/perfume) Higher concentration level components; fragranced product clinically evaluated for irritation
and sensitization potential
Product should be efficacious and should be demonstrated to be well
Other —
tolerated
IL-1α: interleukin-1α, IL-1ra: interleukin-1 receptor antagonist.

Table 3: Proinflammatory activity of commercially available cleansing products.

Cleanser IL-1α (pg/mL) MTT cell proliferation assay


Mild baby cleanser 100.5 ± 35.0 99.5%
Sensitive skin syndet bar 1150.1 ± 0.1 6.5%
Mean (± standard deviation) IL-1α (pg/mL) released from in vitro skin tissue equivalents (EpiDerm, MatTek Corporation, Ashland, MA, USA) after exposure
to various cleansing products. MTT cell proliferation (cell viability) assay data are also shown. The sensitive skin syndet bar had significantly more cell death
than the mild baby cleanser, IL-1α: interleukin-1α.

front, abdomen, and upper leg of neonates who received an provide practical considerations relating to preservative sys-
emollient after taking a bath with liquid cleanser (P < .001 tems, fragrances, and the reasons behind other formulation
for all regions versus infants who bathed with water alone considerations.
and did not receive an emollient after bathing). After 8 weeks, It has been postulated that emollient products containing
median TEWL also was significantly lower on the forehead, a physiologic balance of epidermal lipids (3 : 1 : 1 : 1 molar
abdomen, upper leg, and buttock in neonates who received ratio of cholesterol/ceramide/palmitate/linoleate) are opti-
an emollient after bathing with water alone (P < .001 for all mal for barrier repair [103]. Furthermore, many compounds
listed regions versus infants who bathed with water alone and (used alone or in combination with other molecules) have
did not receive an emollient). Emollient use after bathing been reported to have beneficial effects on skin barrier
with or without a liquid cleanser led to an improvement in function. However, due to the complex nature of emol-
SC hydration on the forehead and abdomen (P < .001 versus lient formulations and differing individual needs, designing
infants who bathed with water alone and did not receive an emollients that are optimized for a particular individual and
emollient). Moreover, use of an emollient did not affect skin tailoring the emollient for maximum efficacy are still active
surface pH or sebum production. areas of research [104].
Many healthcare practitioners and caregivers understand Oils are used traditionally in some countries as emol-
the utility of incorporating mild, appropriately formulated lients during the bathing process [105–109], to treat
cleansers into the bathing routine, yet far fewer caregivers hypothermia in newborns, [110], or to remove impurities
recognize the importance or benefits of emollient use for from neonatal skin hours after birth [111]. Some derma-
application on healthy neonatal and infant skin. In a recent tologists have recommended using bath oils for their ability
study, 90% of the mothers surveyed believed that their to leave a film on the skin surface or to reduce xerosis
child’s skin was not dry, yet clinical evaluation revealed [106–108]. One study [109] found that bath oils can be
that only 37% of these children had nondry skin, whereas beneficial to infants, yet another double-blind, randomized
the remaining children exhibited clinical signs of low to study showed that some bath or shower oils can be irritating
moderately dry skin [102]. to skin [112]. More recently, an analysis of systematic review
found that there was no benefit associated with using oils
7.1. Formulation Considerations. Similar to the case of to treat conditions like atopic eczema [113]. As noted
cleansing products, appropriate formulation of emollient by Shams et al. [113], there is an absence of evidence
products need to take into account the particular nature demonstrating a benefit of using bath emollients in addition
of infant skin properties [7, 11]. Some considerations that to directly applied emollients in the treatment of atopic
may be important when selecting a skin care emollient eczema. Furthermore, Tarr and Iheanacho [114] were not
product are summarized in Table 4. Although this table is able to find a randomized controlled trial that showed the
not meant to be an exhaustive list, we have attempted to benefit of using bath emollients. Although the benefits of
Dermatology Research and Practice 9

Table 4: Practical considerations for emollient product selection.

Efficacy considerations
(i) Appropriate tests should testify to the efficacy of the product formulation
Safety considerations: overall
(i) The margin of safety for each ingredient at the concentration used in the formulation should be considered
(ii) Ingredients in a product can behave differently than in isolation; therefore, it is important to evaluate the full formulation for safety and
potential dermal effects, including irritation and sensitization
Safety considerations: fragrance
(i) The use of fragranced products for healthy neonates and infants should be supported by evidence for safety and tolerance
(ii) Fragrances should be compliant with the International Fragrance Association (IFRA), which is a body that helps to ensure the safety of
fragrance materials
Safety considerations: preservatives
(i) Products should be microbiologically robust
(ii) “Natural” does not always mean safer (e.g., some natural oils (eucalyptus, sage, and tea tree oils) can be toxic at certain levels)
(iii) Preservative ingredients can be natural or synthetic as long as their safety profile is documented; identical chemical structure means
identical safety profile
Safety considerations: labeling and packaging
(i) Directions for product use should communicate and educate parents on safe and appropriate use
(ii) Package design should help to minimize product contamination (e.g., loose top or seal could expose product to microbes)

using oils to improve the skin barrier remain equivocal, bath upper layers of the SC [126], is immiscible with water. It is
oil use may have a soothing or calming effect on infants noncomedogenic [127], has a long record of safe use [128],
when used during massage or bathing [115, 116]. Moreover, and is unlikely to go rancid even in hot, humid climates.
the incorporation of emollients into the bathing routine Mineral oil helps to enhance the skin barrier as shown by
may provide emotional benefits such as reinforcement of the a reduction in TEWL following topical application of the
parental or caregiver bond through touch [29]. oil [126]. By reducing the amount of evaporated water, it
While bath oils may not have an obvious benefit, some helps keep the SC more hydrated, leading to an improved
emollient formulations contain essential fatty acids (e.g., appearance on the skin surface. Other favorable physical
linoleic acid) that can provide systemic benefits to neonates properties of mineral oil include a low viscosity and a low
[117]. Not all vegetable oils are appropriate for use on skin specific gravity relative to water.
[118]. Vegetable oils can vary in composition, for example, The semiocclusive mineral oil layer on the skin surface
in the ratio of linoleic to oleic acid. Some vegetable oils, helps to retain water by retarding water evaporation [126].
including certain olive, soybean, and mustard oils, can be In an unpublished experiment, our group investigated the
detrimental to the integrity of the skin barrier [119]. Some effects of mineral oil on water retention in excised human
unsaturated free fatty acids can act as permeation enhancers SC. Equal weights and sizes of human SC were dehydrated
[120], an effect that may cause contact dermatitis in adults at a constant temperature and humidity for 48 hours. After
[121–124]. In addition, many vegetable oils are unstable dehydration, the weights of the human SC samples were
and degrade by hydrolysis and oxidation. Degradation can recorded. One set of samples (group 1) underwent full
increase the likelihood of microbial growth and spoilage, hydration by placing the samples in a closed chamber (90%
especially in hot, humid environments. Cutaneous Propioni- humidity) for 48 hours. At the end of this period, the “wet”
bacterium acnes and Propionibacterium granulosum secrete sample weight was recorded. A second set of samples (group
lipases, enzymes that hydrolyze sebum triglycerides to free 2) was allowed to equilibrate to room temperature. Once
fatty acids [125]. By extension, Propionibacterium acnes, complete, sample weights in group 2 were recorded. The
Propionibacterium granulosum, and possibly other cutaneous weight of the hydrated samples was calculated by taking
bacteria may hydrolyze vegetable oils present in topicals into the average percentage of the wet sample weight (group
free fatty acids, accelerating the degradation of vegetable oils 1) minus the average percentage of the room equilibrated
on the skin surface. Use of unstable emollients or those that sample weight (group 2). A third set of samples (group 3;
degrade quickly may lead to undesirable effects, especially on control) was maintained at dry weight until use. Mineral oil
infant skin that is undergoing SC maturation and expansion was applied to the fully hydrated samples in group 1, while
of innate immune function. two other moisturizing lotions were applied to the samples in
Emollients that contain inert, stable ingredients such as group 2. Mineral oil and test lotions were weight-adjusted to
mineral oil are preferable for use on the maturing infant skin. ensure that equivalent weights of oil, lotion, and water were
Mineral oil, a semiocclusive ingredient that penetrates the applied to human SC (some of the lotions contained water,
10 Dermatology Research and Practice

whereas mineral oil contained none). Weight measurements It might be further reasonably speculated that increased
were taken immediately after product application on all rates of nosocomial infections could have been due to use
samples; weights also were recorded periodically until there of a preservative-free petrolatum-based ointment that was
was no further decline in sample weight (i.e., complete opened and exposed to pathogenic organisms. Although it
evaporation of SC water). In the absence of mineral oil, is unlikely that a preservative-free petrolatum-based product
SC moisture evaporated quickly, whereas samples with manufactured using good manufacturing practices would
mineral oil showed higher water retention. Figure 2 shows a become contaminated, inadvertent addition of excessive
hypothetical model for how a semiocclusive layer of mineral moisture from a damp environment (i.e., bathroom) could
oil could improve the water barrier. In the left panel, no lead to product contamination. Similar to petrolatum,
mineral oil is present. In the right panel, water evaporation mineral oil is anhydrous, yet there is evidence that it
from the surface of skin slows in the presence of mineral oil, can become contaminated by improper handling [134].
leading to reduced TEWL. Given these considerations, formulators should select an
Another approach to enhance the skin barrier of infant effective preservative system, even when formulating low
skin is to combine the emollient ingredients within the water activity emollients.
liquid cleanser formulation [29]. More studies are needed to Several studies have found very high concentrations
determine specifically which types of emollient formulations (>104 colony-forming units (CFU)/g) of microbial con-
will be optimal for neonatal and infant skin. taminants in consumer products that are poorly preserved
or preservative-free [135, 136]. Use of a poorly preserved,
8. Use of Emollients on Compromised Skin contaminated emollient led to an outbreak of P. aeruginosa
in a neonatal intensive care unit [137]. Furthermore, use
8.1. Premature Infants. Gestational age is strongly linked to of preservative-free white petrolatum has been linked to
epidermal barrier function. The skin barrier of premature systemic candidiasis [138].
infants is injured easily and can serve as a portal of entry Since publication of the meta-analysis in 2004 [132],
for agents, causing serious bacterial infections [13, 129]. other studies have also investigated emollient use in prema-
Several groups have investigated using vegetable seed oils ture infants or neonates. In a randomized controlled trial,
to improve skin barrier function in premature infants of Darmstadt et al. evaluated the efficacy of a petrolatum-based
various ages [28, 100, 119, 130]. Although several studies emollient and a sunflower seed oil with high-linoleate con-
have shown that emollient use can decrease the frequency tent on neonatal mortality rates among hospitalized preterm
of dermatitis or improve skin integrity in very premature infants (≤33 weeks gestation) at a large tertiary hospital
newborns [16, 17, 26, 131], there is controversy about the in Bangladesh [28]. Massaging high-risk infants with the
use and effectiveness of emollients in high-risk neonates and petrolatum-based emollient or the high-linoleate sunflower
infants. seed oil led to a reduction in nosocomial bloodstream
In 2004, Conner et al. [132] reviewed the effectiveness of infections (reduction rates for the respective treatments were
prophylactic application of topical ointments on nosocomial 71% (95% CI: 17%–82%) and 41% (95% CI: 4%–63%)
sepsis rates and other complications in premature births. In relative to no treatment). Moreover, massage with either
their meta-analysis, they included infants (n = 1304) with a product led to a significant decrease in neonatal mortality
gestational age <37 weeks who received an emollient within (32% and 26% for the petrolatum-based emollient and
96 hours of birth. They found that prophylactic application the high-linoleate sunflower seed oil, resp.) relative to the
of topical ointments increased the risk of coagulase negative standard of care for premature neonates (no treatment). In
staphylococcal infection (typical relative risk (RR) 1.31, 95% contrast, use of the same petrolatum-based emollient on
confidence interval (CI) 1.02–1.70; typical risk difference extremely premature infants (birth weight 501 to 1000 g)
0.04, 95% CI 0.00–0.08), any bacterial infection (typical RR in the United States (and other countries) did not have an
1.19, 95% CI 0.97–1.46; typical risk difference 0.04, 95% CI effect on neonatal mortality [131]. Darmstadt et al. [28]
0.01–0.08) and nosocomial infection (typical RR 1.20, 95% proposed that differences in trial design, study population,
CI 1.00–1.43; typical risk difference 0.05, 95% CI 0.00–0.09). treatment (i.e., access to life-saving interventions), and
One limitation of this paper was that it included only four environmental factors could help explain the differences in
studies [16, 17, 26, 131], which reflects the limited number neonatal mortality rates observed between the two studies
of studies that had been published at that time. It remains [28, 131].
to be seen if the conclusions of the meta-analysis would be LeFevre et al. [139] used a Monte Carlo simulation on
applicable for other topicals or emollients. the data generated by Darmstadt et al. [28] and found that
In the studies that observed higher rates of infection use of the petrolatum-based emollient or sunflower seed oil
[16, 26, 131], several possible explanations have been with high-linoleate content was a cost-effective strategy to
proffered as to the cause. Conner et al. [132] speculate improve clinical outcomes. Relative to untreated premature
that contamination may have occurred during application infants, the petrolatum-based emollient and sunflower seed
of the preservative-free petrolatum ointment or that its oil had respective costs of US$162 and US$61 per death
use may lead to conditions suitable to proliferation of averted and respective costs of US$5.74 and US$2.15 per year
bacterial organisms. Visscher [133] posits that skin occlusion of life lost averted [139]. Although both products were cost-
on extremely low birth weight neonates may have delayed effective strategies to reduce neonatal mortality in a hospital
barrier maturation. setting, it is not known whether a reduction in mortality
Dermatology Research and Practice 11

(a) (b)

Figure 2: Stratum corneum (SC) moisture retention following application of mineral oil emollient. In (a), transepidermal water loss (TEWL)
from the SC is shown under ambient temperature, humidity, and pressure. In (b), TEWL is reduced following emollient application. Oils in
the emollient create a semiocclusive layer. The reduction in water evaporation leads to greater water retention in the SC.

also would be observed in a low-resource community setting prophylactic use of emollients that are appropriately formu-
outside the hospital, which is more typical of a normal lated for use after birth may produce measurable benefits
birthing environment in Bangladesh and other developing later in life. To test this hypothesis, some members of our
countries [140]. team conducted a 6-week study on 51 infants (aged 3 to
Brandon et al. compared the effects of a composition 12 months) that consisted of giving the infant participants
containing water, polymers, and odorless, nonalcoholic twice-daily baths with a mild baby cleanser, followed by
evaporating agents or a petrolatum-based emollient on twice-daily application of one of three marketed lotions
skin barrier integrity over the first two weeks of life in (unpublished data). Infants were randomized to receive
premature (<33 weeks gestation) infants [141]. A nine-point one of three oil-in-water emollient formulations, each of
neonatal skin condition score (NSCS) was used to assess which contained different types of surfactants and other
skin dryness, erythema, and skin breakdown. TEWL declined ingredients. Skin barrier function was assessed indirectly by
significantly over time; there were no differences in TEWL measuring TEWL and SC hydration (skin conductance) on
between treatment groups. The neonatal skin condition the upper volar arm and lower dorsal arm. The effect of
scores for infants receiving the petrolatum-based emollient each lotion varied among the three groups. Results indicated
were statistically better than those for infants receiving the that skin barrier function and SC hydration improved with
aqueous polymeric composition, yet both scores were within daily use of only one of the emollients over a period of six
normal range. Few infants in either treatment group had skin weeks. These results suggest that emollient efficacy is related
breakdown. to the specific chemistry and ingredients of the formulation.
Although many studies have investigated the use of Although no studies have investigated the long-term use
emollients in children or adults with eczema or AD, very of emollients on infants, long-term emollient use could
few studies have investigated the use of emollients in healthy, improve the epidermal skin barrier and improve overall skin
premature, or full-term neonates. A summary of studies that condition relative to untreated skin.
have investigated the use of emollients in healthy, preterm or
full-term neonates (0–4 weeks old) or infants (1–6 months
old) is shown in Table 5. 10. Summary
Although the need for and benefits of good skin hygiene
are clear, recommendations for best cleansing and bathing
9. Emollient Use May Lead to Long-Term practices remain debated during infancy and early child-
Improvement in Skin Condition hood. As infant skin continues to change throughout the
first years of life, its dynamic properties need to be addressed
To our knowledge, there are no randomized controlled trials with appropriate skin care routines. Use of mild surfactant
that have investigated the long-term use of emollients on systems in cleansers can enable maintenance of skin barrier
skin barrier function or overall skin condition. Nevertheless, integrity; these cleansers may also be minimally disruptive to
12

Table 5: Emollient therapy in healthy, full-term, or premature neonates (0–4 weeks old) or infants (1–6 months old) on skin barrier function: literature review† .

Healthy, full-term infants


Endpoints/
Study Cohort Treatment Study duration Primary outcome(s)
measurements
Wash with emollient
Body wash; body wash with improved skin condition;
64 healthy, full-term neonates TEWL, SC hydration, skin
emollient use after bathing; water in some cases, lower TEWL
Garcia Bartels et al. [19] (gestation ≥37 weeks aged ≤48 8 weeks surface pH, sebum, NSCS, and
alone, followed by emollient after and higher SC hydration
hours) bacterial colonization
bathing were observed; no adverse
events
Reduced TEWL in both
44 healthy, full-term infants Lotion was applied after a
Garcia Bartels et al. TEWL, SC hydration, skin groups; site-specific
(≥37 weeks gestation) aged 3–6 swimming lesson once weekly or 5 weeks
[146] surface pH, and sebum differences in the treatment
months old no treatment
group were observed
Emollient consisting of
10 healthy, full-term neonates
ceramides, cholesterol, and free
(0–4 weeks old; gestation ≥36 TEWL, SC hydration, skin Emollient use reduced
Lowe et al. [147] fatty acids at a 3 : 1 : 1 ratio and 6 weeks
weeks) with a family history of surface pH, and sebum TEWL
2% petrolatum (applied once
allergic disease
daily)
Skin barrier measurements
22 full-term infants (≥37 weeks
remained within normal
gestation) considered to be at Oil-in-water, petrolatum-based
Simpson et al. [20] Up to 2 years TEWL and skin capacitance range; only three
high risk for developing atopic emollient cream
participants developed
dermatitis
atopic dermatitis
Premature Infants
The petrolatum-based
emollient led to a
Petrolatum-based emollient significant reduction in the
Fluids, electrolytes, bilirubin,
Beeram et al. [18] 54 infants (≤27 weeks gestation) applied every 6 hours or no 2 weeks need for fluids; it also led to
and sepsis
treatment better urine output, more
stable electrolytes, and
lower bilirubin values
Polymer, liquid-based film
Both treatments were well
(applied twice) or Total fluid intake, TEWL, and
Brandon et al. [141] 69 infants (<33 weeks gestation) 2 weeks tolerated; both led to a
petrolatum-based emollient neonatal skin condition
decrease in TEWL
(twice-daily application)
Dermatology Research and Practice
Table 5: Continued.
Healthy, full-term infants
Endpoints/
Study Cohort Treatment Study duration Primary outcome(s)
measurements
Sunflower seed oil and
petrolatum-based
Sunflower seed oil or
emollient reduced
petrolatum-based emollient (3
Dermatology Research and Practice

Darmstadt et al. 497 premature infants (≤72 Survival rate and rate of mortality by 25–30%;
times daily for 14 days, then ≥14 days
[28, 100, 148] hours old; gestation ≤33 weeks) nosocomial infection sunflower seed oil reduced
twice daily until hospital
nosocomial infection rates
discharge) or no treatment
by a statistically significant
margin
Emollient decreased
dermatitis of the hands
Twice-daily application of a
34 neonates (29–36 weeks TEWL, NSCS, and quantitative (days 2–11), feet (days
Lane and Drost [16] water-in-oil emollient; no 16 days
gestation) microbiology 2–16), and abdomen (days
treatment
7–11); no changes in
microbial flora
Emollient use led to
statistically significant
decrease in TEWL;
significant improvement in
Temperature, TEWL, fluid
infant skin condition on
Petrolatum-based emollient intake, weight analysis, skin
60 neonates (<33 weeks days 7 and 14; less
Nopper et al. [17] (applied twice daily); no 2 weeks condition, microbiology, and
gestation) colonization of the axilla
treatment blood/urine analysis for
on days 2, 3, 4, and 14;
cerebrospinal fluid cultures
statistically significant
reduction of positive
findings in blood and
cerebrospinal fluid
TEWL: transepidermal water loss, SC: stratum corneum, NSCS: neonatal skin condition score.
† Studies published between 1 January 1960 and 1 June 2012 were identified by searching peer-reviewed literature indexed in PubMed. The titles and abstracts of indexed publications listed in PubMed were searched

using the following words: “newborn OR neonat∗ OR infant∗ ” (group 1), “emollient OR lotion OR cream OR topical” (group 2), and “skin” (group 3). These three groupings were connected using the Boolean
operators “AND”. The titles and abstracts were also searched using the word “vitro” and the Boolean operator “NOT”. Finally, only the titles of PubMed-indexed publications were searched using a fifth group of
words and were connected to the search string using the Boolean operator “NOT”: “injury OR wound OR burn OR damage OR eczema OR dermatitis OR psoriasis OR disease∗ OR pain OR hemangioma∗ OR
syndrome OR sepsis OR antisepsis.” Review articles, publications that were printed in a language other than English were also excluded. Although our search generated 220 publications, only 9 (summarized in
Table 5) met the search criteria described above.
13
14 Dermatology Research and Practice

skin surface pH and have minimal potential to stimulate the continue to develop through the first year of life,” The Journal
production of IL-1α and other proinflammatory molecules. of Investigative Dermatology, vol. 128, no. 7, pp. 1728–1736,
Emollients can provide benefits to premature infants or 2008.
infants with compromised skin barrier function. Few studies [12] K. A. Capone, S. E. Dowd, G. N. Stamatas, and J. Nikolovski,
to date have demonstrated the benefits of emollient use on “Diversity of the human skin microbiome early in life,” The
healthy, full-term infants. In addition to providing short- Journal of Investigative Dermatology, vol. 131, no. 10, pp.
term benefits such as maintaining or improving skin barrier 2026–2032, 2011.
function, it is hypothesized that long-term use of emollients [13] Y. N. Kalia, L. B. Nonato, C. H. Lund, and R. H. Guy,
may produce lasting benefits to skin barrier function and “Development of skin barrier function in premature infants,”
The Journal of Investigative Dermatology, vol. 111, no. 2, pp.
overall skin condition. In the future, harmonization of
320–326, 1998.
neonatal and infant skin care guidelines—including use of
[14] S. Verdier-Sévrain and F. Bonté, “Skin hydration: a review on
properly formulated cleansers and emollients—is warranted.
its molecular mechanisms,” Journal of Cosmetic Dermatology,
vol. 6, no. 2, pp. 75–82, 2007.
Acknowledgment [15] L. Walker, S. Downe, and L. Gomez, “Skin care in the well
term newborn: two systematic reviews,” Birth, vol. 32, no. 3,
The authors thank Russel M. Walters, Ph.D. for providing pp. 224–228, 2005.
technical expertise on cleansers and surfactants and for his [16] A. T. Lane and S. S. Drost, “Effects of repeated application of
assistance with the IL-1α and MTT cell proliferation assay emollient cream to premature neonates’ skin,” Pediatrics, vol.
data. 92, no. 3, pp. 415–419, 1993.
[17] A. J. Nopper, K. A. Horii, S. Sookdeo-Drost, T. H. Wang, A. J.
Mancini, and A. T. Lane, “Topical ointment therapy benefits
References premature infants,” The Journal of Pediatrics, vol. 128, no. 5,
[1] Y. B. Chiou and U. Blume-Peytavi, “Stratum corneum part 1, pp. 660–669, 1996.
maturation. A review of neonatal skin function,” Skin Phar- [18] M. Beeram, R. Olvera, D. Krauss, C. Loughran, and M. Petty,
macology and Physiology, vol. 17, no. 2, pp. 57–66, 2004. “Effects of topical emollient therapy on infants at or less
[2] G. N. Stamatas, J. Nikolovski, M. A. Luedtke, N. Kollias, and than 27 weeks’ gestation,” Journal of the National Medical
B. C. Wiegand, “Infant skin microstructure assessed in vivo Association, vol. 98, no. 2, pp. 261–264, 2006.
differs from adult skin in organization and at the cellular [19] N. Garcia Bartels, R. Scheufele, F. Prosch et al., “Effect of
level,” Pediatric Dermatology, vol. 27, no. 2, pp. 125–131, standardized skin care regimens on neonatal skin barrier
2010. function in different body areas,” Pediatric Dermatology, vol.
27, no. 1, pp. 1–8, 2010.
[3] A. A. Larson and J. G. H. Dinulos, “Cutaneous bacterial infec-
tions in the newborn,” Current Opinion in Pediatrics, vol. 17, [20] E. L. Simpson, T. M. Berry, P. A. Brown, and J. M. Hanifin, “A
no. 4, pp. 481–485, 2005. pilot study of emollient therapy for the primary prevention
of atopic dermatitis,” Journal of the American Academy of
[4] U. Meyer-Hoffert, A. Zimmermann, M. Czapp et al., “Flag-
Dermatology, vol. 63, no. 4, pp. 587–593, 2010.
ellin delivery by Pseudomonas aeruginosa rhamnolipids
induces the antimicrobial protein psoriasin in human skin,” [21] R. M. Walters, M. J. Fevola, J. J. LiBrizzi, and K. Martin,
PLoS ONE, vol. 6, no. 1, Article ID e16433, 2011. “Designing cleansers for the unique needs of baby skin,”
Cosmetics & Toiletries, vol. 123, no. 12, pp. 53–60, 2008.
[5] P. M. Elias, “The skin barrier as an innate immune element,”
[22] N. J. McNally, H. C. Williams, D. R. Phillips et al., “Atopic
Seminars in Immunopathology, vol. 29, no. 1, pp. 3–14, 2007.
eczema and domestic water hardness,” The Lancet, vol. 352,
[6] G. Yosipovitch, A. Maayan-Metzger, P. Merlob, and L. Sirota, no. 9127, pp. 527–531, 1998.
“Skin barrier properties in different body areas in neonates,”
[23] Y. Miyake, T. Yokoyama, A. Yura, M. Iki, and T. Shimizu,
Pediatrics, vol. 106, no. 1, part 1, pp. 105–108, 2000.
“Ecological association of water hardness with prevalence
[7] G. N. Stamatas, J. Nikolovski, M. C. Mack, and N. Kollias, of childhood atopic dermatitis in a Japanese urban area,”
“Infant skin physiology and development during the first Environmental Research, vol. 94, no. 1, pp. 33–37, 2004.
years of life: a review of recent findings based on in vivo [24] K. S. Thomas, T. Dean, C. O’Leary et al., “A randomised
studies,” International Journal of Cosmetic Science, vol. 33, no. controlled trial of ion-exchange water softeners for the
1, pp. 17–24, 2011. treatment of eczema in children,” PLoS Medicine, vol. 8, no.
[8] S. B. Hoath and H. I. Maibach, Neonatal Skin: Structure and 2, Article ID e1000395, 2011.
Function, Marcel Dekker, New York, NY, USA, 2nd edition, [25] K. S. Thomas, K. Koller, T. Dean et al., “A multicentre
2003. randomised controlled trial and economic evaluation of ion-
[9] N. J. Evans and N. Rutter, “Development of the epidermis in exchange water softeners for the treatment of eczema in
the newborn,” Biology of the Neonate, vol. 49, no. 2, pp. 74– children: the Softened Water Eczema Trial (SWET),” Health
80, 1986. Technology Assessment, vol. 15, no. 8, pp. v-vi, 1–156, 2011.
[10] J. W. Fluhr, R. Darlenski, A. Taieb et al., “Functional skin [26] R. C. Pabst, K. P. Starr, S. Qaiyumi, R. S. Schwalbe, and I.
adaptation in infancy—almost complete but not fully com- H. Gewolb, “The effect of application of Aquaphor on skin
petent,” Experimental Dermatology, vol. 19, no. 6, pp. 483– condition, fluid requirements, and bacterial colonization in
492, 2010. very low birth weight infants,” Journal of Perinatology, vol.
[11] J. Nikolovski, G. N. Stamatas, N. Kollias, and B. C. Wiegand, 19, no. 4, pp. 278–283, 1999.
“Barrier function and water-holding and transport proper- [27] I. Buraczewska, B. Berne, M. Lindberg, H. Törmä, and M.
ties of infant stratum corneum are different from adult and
Dermatology Research and Practice 15

Lodén, “Changes in skin barrier function following long- hydration levels,” The Journal of Investigative Dermatology,
term treatment with moisturizers, a randomized controlled vol. 120, no. 5, pp. 750–758, 2003.
trial,” The British Journal of Dermatology, vol. 156, no. 3, pp. [43] J. Sato, M. Yanai, T. Hirao, and M. Denda, “Water content and
492–498, 2007. thickness of the stratum corneum contribute to skin surface
[28] G. L. Darmstadt, S. K. Saha, A. S. M. N. U. Ahmed et al., morphology,” Archives of Dermatological Research, vol. 292,
“Effect of skin barrier therapy on neonatal mortality rates no. 8, pp. 412–417, 2000.
in preterm infants in Bangladesh: a randomized, controlled, [44] G. E. Pierard, V. Goffin, T. Hermanns-Le, and C. Pierard-
clinical trial,” Pediatrics, vol. 121, no. 3, pp. 522–529, 2008. Franchimont, “Corneocyte desquamation,” International
[29] U. Blume-Peytavi, M. J. Cork, J. Faergemann, J. Szczapa, Journal of Molecular Medicine, vol. 6, no. 2, pp. 217–221,
F. Vanaclocha, and C. Gelmetti, “Bathing and cleansing in 2000.
newborns from day 1 to first year of life: recommendations [45] M. Engelke, J. M. Jensen, S. Ekanayake-Mudiyanselage, and
from a European round table meeting,” Journal of the E. Proksch, “Effects of xerosis and ageing on epidermal
European Academy of Dermatology and Venereology, vol. 23, proliferation and differentiation,” The British Journal of
no. 7, pp. 751–759, 2009. Dermatology, vol. 137, no. 2, pp. 219–225, 1997.
[30] J. A. Fairley and J. E. Rasmussen, “Comparison of stratum [46] V. Rogiers and EEMCO Group, “EEMCO guidance for
corneum thickness in children and adults,” Journal of the the assessment of transepidermal water loss in cosmetic
American Academy of Dermatology, vol. 8, no. 5, pp. 652–654, sciences,” Skin Pharmacology and Applied Skin Physiology,
1983. vol. 14, no. 2, pp. 117–128, 2001.
[31] S. Saijo and H. Tagami, “Dry skin of newborn infants: [47] F. Rippke, V. Schreiner, and H. J. Schwanitz, “The acidic
functional analysis of the stratum corneum,” Pediatric Der- milieu of the horny layer: new findings on the physiology and
matology, vol. 8, no. 2, pp. 155–159, 1991. pathophysiology of skin pH,” American Journal of Clinical
[32] P. H. Hoeger and C. C. Enzmann, “Skin physiology of the Dermatology, vol. 3, no. 4, pp. 261–272, 2002.
neonate and young infant: a prospective study of functional [48] C. Lund, J. Kuller, A. Lane, J. W. Lott, and D. A. Raines,
skin parameters during early infancy,” Pediatric Dermatology, “Neonatal skin care: the scientific basis for practice,” Neona-
vol. 19, no. 3, pp. 256–262, 2002. tal Network, vol. 18, no. 4, pp. 15–27, 1999.
[33] M. O. Visscher, R. Chatterjee, K. A. Munson, W. L. Pickens, [49] H. Lambers, S. Piessens, A. Bloem, H. Pronk, and P. Finkel,
and S. B. Hoath, “Changes in diapered and nondiapered “Natural skin surface pH is on average below 5, which
infant skin over the first month of life,” Pediatric Dermatol- is beneficial for its resident flora,” International Journal of
ogy, vol. 17, no. 1, pp. 45–51, 2000. Cosmetic Science, vol. 28, no. 5, pp. 359–370, 2006.
[34] F. Giusti, A. Martella, L. Bertoni, and S. Seidenari, “Skin [50] D. F. Askin, “Bacterial and fungal infections in the neonate,”
barrier, hydration, and pH of the skin of infants under 2 years Journal of Obstetric, Gynecologic, and Neonatal Nursing, vol.
of age,” Pediatric Dermatology, vol. 18, no. 2, pp. 93–96, 2001. 24, no. 7, pp. 635–643, 1995.
[35] I. Wanke, H. Steffen, C. Christ et al., “Skin commensals [51] F. Schultz Larsen, T. Diepgen, and A. Svensson, “The occur-
amplify the innate immune response to pathogens by rence of atopic dermatitis in North Europe: an international
activation of distinct signaling pathways,” The Journal of questionnaire study,” Journal of the American Academy of
Investigative Dermatology, vol. 131, no. 2, pp. 382–390, 2011. Dermatology, vol. 34, no. 5, part 1, pp. 760–764, 1996.
[36] K. Hanley, Y. Jiang, P. M. Elias, K. R. Feingold, and M. L. [52] D. Laughter, J. A. Istvan, S. J. Tofte, and J. M. Hanifin, “The
Williams, “Acceleration of barrier ontogenesis in vitro prevalence of atopic dermatitis in Oregon schoolchildren,”
through air exposure,” Pediatric Research, vol. 41, no. 2, pp. Journal of the American Academy of Dermatology, vol. 43, no.
293–299, 1997. 4, pp. 649–655, 2000.
[37] A. V. Rawlings, “Trends in stratum corneum research and the [53] Y. L. V. A. Werner and M. Lindberg, “Transepidermal water
management of dry skin conditions,” International Journal of loss in dry and clinically normal skin in patients with atopic
Cosmetic Science, vol. 25, no. 1-2, pp. 63–95, 2003. dermatitis,” Acta Dermato-Venereologica, vol. 65, no. 2, pp.
[38] A. V. Rawlings, L. R. Scott, C. R. Harding, and P. A. Bowser, 102–105, 1985.
“Stratum corneum moisturization at the molecular level,” [54] S. Seidenari and G. Giusti, “Objective assessment of the
The Journal of Investigative Dermatology, vol. 103, no. 5, pp. skin of children affected by atopic dermatitis: a study of
731–740, 1994. pH, capacitance and TEWL in eczematous and clinically
[39] M. Machado, T. M. Salgado, J. Hadgraft, and M. E. Lane, uninvolved skin,” Acta Dermato-Venereologica, vol. 75, no. 6,
“The relationship between transepidermal water loss and pp. 429–433, 1995.
skin permeability,” International Journal of Pharmaceutics, [55] H. Ogawa and T. Yoshiike, “Atopic dermatitis: studies of skin
vol. 384, no. 1-2, pp. 73–77, 2010. permeability and effectiveness of topical PUVA treatment,”
[40] A. Rawlings, C. Harding, A. Watkinson, J. Banks, C. Ack- Pediatric Dermatology, vol. 9, no. 4, pp. 383–385, 1992.
erman, and R. Sabin, “The effect of glycerol and humidity [56] H. H. Kong, J. Oh, C. Deming et al., “Temporal shifts in the
on desmosome degradation in stratum corneum,” Archives of skin microbiome associated with disease flares and treatment
Dermatological Research, vol. 287, no. 5, pp. 457–464, 1995. in children with atopic dermatitis,” Genome Research, vol. 22,
[41] H. Tagami, Y. Kanamaru, K. Inoue et al., “Water sorption- no. 5, pp. 850–859, 2012.
desorption test of the skin in vivo for functional assessment [57] B. Schittek, “The antimicrobial skin barrier in patients with
of the stratum corneum,” The Journal of Investigative Derma- atopic dermatitis,” Current Problems in Dermatology, vol. 41,
tology, vol. 78, no. 5, pp. 425–428, 1982. pp. 54–67, 2011.
[42] J. A. Bouwstra, A. de Graaff, G. S. Gooris, J. Nijsse, J. W. [58] M. Lebwohl and L. G. Herrmann, “Impaired skin barrier
Wiechers, and A. C. van Aelst, “Water distribution and
related morphology in human stratum corneum at different
16 Dermatology Research and Practice

function in dermatologic disease and repair with moisturiza- [74] C. Lund, J. Kuller, D. Raines, S. Ecklund, M. Archam-
tion,” Cutis; Cutaneous Medicine for the Practitioner, vol. 76, bault, and P. O’Flaherty, Neonatal Skin Care, Associa-
no. 6, supplement, pp. 7–12, 2005. tion of Women’s Health, Obstetric and Neonatal Nurses
[59] J. M. Hanifin, K. D. Cooper, V. C. Ho et al., “Guidelines (AWHONN), Washington, DC, USA, 2nd edition, 2007.
of care for atopic dermatitis, developed in accordance with [75] National Collaborating Centre for Primary Care, “NICE
the American Academy of Dermatology (AAD)/American clinical guideline 37. Routine postnatal care of women
Academy of Dermatology Association ‘Administrative Reg- and their babies,” National Institute for Health and Clin-
ulations for Evidence-Based Clinical Practice Guidelines’,” ical Excellence, London, UK, 2006, http://www.nice.org
Journal of the American Academy of Dermatology, vol. 50, no. .uk/nicemedia/live/10988/30144/30144.pdf.
3, pp. 391–404, 2004. [76] C. Gelmetti, “Skin cleansing in children,” Journal of the
[60] National Collaborating Centre for Women’s and Children’s European Academy of Dermatology and Venereology, vol. 15,
Health, “NICE clinical guideline 57. Atopic eczema in supplement 1, pp. 12–15, 2001.
children,” National Institute for Health and Clinical Excel- [77] B. L. Kuehl, K. S. Fyfe, and N. H. Shear, “Cutaneous
lence, London, UK, 2007, http://www.nice.org.uk/niceme- cleansers,” Skin Therapy Letter, vol. 8, no. 3, pp. 1–4, 2003.
dia/live/11901/38597/38597.pdf. [78] F. S. Afsar, “Skin care for preterm and term neonates,”
[61] K. L. E. Hon, K. Y. Wong, L. K. Cheung et al., “Efficacy Clinical and Experimental Dermatology, vol. 34, no. 8, pp.
and problems associated with using a wet-wrap garment 855–858, 2009.
for children with severe atopic dermatitis,” The Journal of [79] R. Gfatter, P. Hackl, and F. Braun, “Effects of soap and
Dermatological Treatment, vol. 18, no. 5, pp. 301–305, 2007. detergents on skin surface pH, stratum corneum hydration
[62] H. Cox, K. Lloyd, H. Williams et al., “Emollients, education and fat content in infants,” Dermatology, vol. 195, no. 3, pp.
and quality of life: the RCPCH care pathway for children with 258–262, 1997.
eczema,” Archives of Disease in Childhood, vol. 96, supplement [80] G. L. Darmstadt and J. G. Dinulos, “Neonatal skin care,”
2, pp. i19–i24, 2011. Pediatric Clinics of North America, vol. 47, no. 4, pp. 757–782,
[63] G. N. Stamatas, C. Zerweck, G. Grove, and K. M. Martin, 2000.
“Documentation of impaired epidermal barrier in mild [81] K. P. Ananthapadmanabhan, D. J. Moore, K. Subramanyan,
and moderate diaper dermatitis in vivo using noninvasive M. Misra, and F. Meyer, “Cleansing without compromise: the
methods,” Pediatric Dermatology, vol. 28, no. 2, pp. 99–107, impact of cleansers on the skin barrier and the technology of
2011. mild cleansing,” Dermatologic Therapy, vol. 17, supplement
[64] S. Adalat, D. Wall, and H. Goodyear, “Diaper dermatitis- 1, pp. 16–25, 2004.
frequency and contributory factors in hospital attending [82] E. C. Siegfried and P. Y. Shah, “Skin care practices in the
children,” Pediatric Dermatology, vol. 24, no. 5, pp. 483–488, neonatal nursery: a clinical survey,” Journal of Perinatology,
2007. vol. 19, no. 1, pp. 31–39, 1999.
[65] D. J. Atherton, “The aetiology and management of irritant [83] M. V. Dizon, C. Galzote, R. Estanislao, N. Mathew, and R.
diaper dermatitis,” Journal of the European Academy of Sarkar, “Tolerance of baby cleansers in infants: a randomized
Dermatology and Venereology, vol. 15, supplement 1, pp. 1– controlled trial,” Indian Pediatrics, vol. 47, no. 11, pp. 959–
4, 2001. 963, 2010.
[66] M. O. Visscher, R. Chatterjee, K. A. Munson, D. E. Bare, and [84] H. Löffler and R. Happle, “Profile of irritant patch testing
S. B. Hoath, “Development of diaper rash in the newborn,” with detergents: sodium lauryl sulfate, sodium laureth sulfate
Pediatric Dermatology, vol. 17, no. 1, pp. 52–57, 2000. and alkyl polyglucoside,” Contact Dermatitis, vol. 48, no. 1,
[67] D. J. Atherton, “A review of the pathophysiology, prevention pp. 26–32, 2003.
and treatment of irritant diaper dermatitis,” Current Medical [85] V. Charbonnier, B. M. Morrison Jr., M. Paye, and H. I.
Research and Opinion, vol. 20, no. 5, pp. 645–649, 2004. Maibach, “Subclinical, non-erythematous irritation with an
[68] A. K. Gupta and A. R. Skinner, “Management of diaper open assay model (washing): sodium lauryl sulfate (SLS)
dermatitis,” International Journal of Dermatology, vol. 43, no. versus sodium laureth sulfate (SLES),” Food and Chemical
11, pp. 830–834, 2004. Toxicology, vol. 39, no. 3, pp. 279–286, 2001.
[69] N. Scheinfeld, “Diaper dermatitis: a review and brief survey [86] V. C. Robinson, W. F. Bergfeld, D. V. Belsito et al., “Final
of eruptions of the diaper area,” American Journal of Clinical report of the amended safety assessment of sodium laureth
Dermatology, vol. 6, no. 5, pp. 273–281, 2005. sulfate and related salts of sulfated ethoxylated alcohols,”
[70] H. T. Shin, “Diaper dermatitis that does not quit,” Dermato- International Journal of Toxicology, vol. 29, no. 4, supplement,
logic Therapy, vol. 18, no. 2, pp. 124–135, 2005. pp. 151S–161S, 2010.
[71] S. Humphrey, J. N. Bergman, and S. Au, “Practical manage- [87] K. Subramanyan, “Role of mild cleansing in the management
ment strategies for diaper dermatitis,” Skin Therapy Letter, of patient skin,” Dermatologic Therapy, vol. 17, supplement 1,
vol. 11, no. 7, pp. 1–6, 2006. pp. 26–34, 2004.
[72] “American Academy of Pediatrics Committee on Fetus and [88] M. J. Fevola, R. M. Walters, and J. J. LiBrizzi, “A new
Newborn. Skin care of newborns,” Pediatrics, vol. 54, no. 6, approach to formulating mild cleansers: hydrophobically-
pp. 682–683, 1974. modified polymers for irritation mitigation,” in Polymeric
[73] A. Bergström, R. Byaruhanga, and P. Okong, “The impact of Delivery of Therapeutics, pp. 221–242, American Chemical
newborn bathing on the prevalence of neonatal hypothermia Society, 2010.
in Uganda: a randomized, controlled trial,” Acta Paediatrica, [89] M. I. White, D. M. Jenkinson, and D. H. Lloyd, “The effect of
International Journal of Paediatrics, vol. 94, no. 10, pp. 1462– washing on the thickness of the stratum corneum in normal
1467, 2005. and atopic individuals,” The British Journal of Dermatology,
vol. 116, no. 4, pp. 525–530, 1987.
Dermatology Research and Practice 17

[90] J. L. Parra, M. Paye, and EEMCO Group, “EEMCO guidance 367–369, 1961.
for the in vivo assessment of skin surface pH,” Skin Pharma- [106] J. W. Stanfield, J. Levy, A. A. Kyriakopoulos, and P. M.
cology and Applied Skin Physiology, vol. 16, no. 3, pp. 188– Waldman, “A new technique for evaluating bath oil in the
202, 2003. treatment of dry skin,” Cutis; Cutaneous Medicine for the
[91] M. L. Chollopetz da Cunha and R. S. Procianoy, “Effect Practitioner, vol. 28, no. 4, pp. 458–460, 1981.
of bathing on skin flora of preterm newborns,” Journal of [107] I. M. Stender, C. Blichmann, and J. Serup, “Effects of oil and
Perinatology, vol. 25, no. 6, pp. 375–379, 2005. water baths on the hydration state of the epidermis,” Clinical
[92] R. L. Gallo, T. Nakatsuji, and EEMCO Group, “Microbial and Experimental Dermatology, vol. 15, no. 3, pp. 206–209,
symbiosis with the innate immune defense system of the 1990.
skin,” The Journal of Investigative Dermatology, vol. 131, no. [108] S. Hill and C. Edwards, “A comparison of the effects of bath
10, pp. 1974–1980, 2011. additives on the barrier function of skin in normal volunteer
[93] L. P. Bernhofer, S. Barkovic, Y. Appa, and K. M. Martin, subjects,” The Journal of Dermatological Treatment, vol. 13,
“IL-1α and IL-1ra secretion from epidermal equivalents and no. 1, pp. 15–18, 2002.
the prediction of the irritation potential of mild soap and [109] B. I. Bettzuege-Pfaff and A. Melzer, “Treating dry skin and
surfactant-based consumer products,” Toxicology In Vitro, pruritus with a bath oil containing soya oil and lauromacro-
vol. 13, no. 2, pp. 231–239, 1999. gols,” Current Medical Research and Opinion, vol. 21, no. 11,
[94] L. P. Bernhofer, M. Seiberg, and K. M. Martin, “The influence pp. 1735–1739, 2005.
of the response of skin equivalent systems to topically applied [110] T. A. Ogunlesi, O. B. Ogunfowora, and M. M. Ogundeyi,
consumer products by epithelial-mesenchymal interactions,” “Prevalence and risk factors for hypothermia on admission in
Toxicology In Vitro, vol. 13, no. 2, pp. 219–229, 1999. Nigerian babies <72 h of age,” Journal of Perinatal Medicine,
[95] T. Hirao, H. Aoki, T. Yoshida, Y. Sato, and H. Kamoda, vol. 37, no. 2, pp. 180–184, 2009.
“Elevation of interleukin 1 receptor antagonist in the stratum [111] F. A. Iweze, “Taboos of childbearing and child-rearing in
corneum of sun-exposed and ultraviolet B-irradiated human Bendel state of Nigeria,” Journal of Nurse-Midwifery, vol. 28,
skin,” The Journal of Investigative Dermatology, vol. 106, no. no. 3, pp. 31–33, 1983.
5, pp. 1102–1107, 1996. [112] M. Lodén, I. Buraczewska, and F. Edlund, “Irritation poten-
[96] M. A. Perkins, M. A. Osterhues, M. A. Farage, and M. K. tial of bath and shower oils before and after use: a double-
Robinson, “A noninvasive method to assess skin irritation blind randomized study,” The British Journal of Dermatology,
and compromised skin conditions using simple tape adsorp- vol. 150, no. 6, pp. 1142–1147, 2004.
tion of molecular markers of inflammation,” Skin Research [113] K. Shams, D. J. C. Grindlay, and H. C. Williams, “What’s new
and Technology, vol. 7, no. 4, pp. 227–237, 2001. in atopic eczema? An analysis of systematic reviews published
[97] T. Terui, T. Hirao, Y. Sato et al., “An increased ratio in 2009-2010,” Clinical and Experimental Dermatology, vol.
of interleukin-1 receptor antagonist to interleukin-1α in 36, no. 6, pp. 573–578, 2011.
inflammatory skin diseases,” Experimental Dermatology, vol. [114] A. Tarr and I. Iheanacho, “Should we use bath emollients for
7, no. 6, pp. 327–334, 1998. atopic eczema?” British Medical Journal, vol. 339, Article ID
[98] V. Goffin, M. Paye, and G. E. Piérard, “Comparison of in vitro b4273, 2009.
predictive tests for irritation induced by anionic surfactants,” [115] T. Field, S. Schanberg, M. Davalos, and J. Malphurs, “Massage
Contact Dermatitis, vol. 33, no. 1, pp. 38–41, 1995. with oil has more positive effects on normal infants,” Pre- and
[99] L. F. Eichenfield and C. A. Hardaway, “Neonatal dermatol- Perinatal Psychology Journal, vol. 11, no. 2, pp. 75–80, 1996.
ogy,” Current Opinion in Pediatrics, vol. 11, no. 5, pp. 471– [116] T. Field, T. Field, C. Cullen et al., “Lavender bath oil reduces
474, 1999. stress and crying and enhances sleep in very young infants,”
[100] G. L. Darmstadt, S. K. Saha, A. S. M. N. U. Ahmed et Early Human Development, vol. 84, no. 6, pp. 399–401, 2008.
al., “Effect of topical treatment with skin barrier-enhancing [117] Z. Friedman, S. J. Shochat, M. J. Maisels, K. H. Marks, and E.
emollients on nosocomial infections in preterm infants in L. Lamberth Jr., “Correction of essential fatty acid deficiency
Bangladesh: a randomised controlled trial,” The Lancet, vol. in newborn infants by cutaneous application of sunflower
365, no. 9464, pp. 1039–1045, 2005. seed oil,” Pediatrics, vol. 58, no. 5, pp. 650–654, 1976.
[101] N. Schürer, V. Schliep, and M. L. Williams, “Differential [118] G. M. M. El Maghraby, M. Campbell, and B. C. Finnin,
utilization of linoleic and arachidonic acid by cultured “Mechanisms of action of novel skin penetration enhancers:
human keratinocytes,” Skin Pharmacology, vol. 8, no. 1-2, pp. phospholipid versus skin lipid liposomes,” International
30–40, 1995. Journal of Pharmaceutics, vol. 305, no. 1-2, pp. 90–104, 2005.
[102] N. K. Tierney and G. N. Stamatas, “Update on infant [119] G. L. Darmstadt, M. Mao-Qiang, E. Chi et al., “Impact of
skin with special focus on dryness and the impact of topical oils on the skin barrier: possible implications for
moisturizers,” in Treatment of Dry Skin Syndrome, M. Lodén neonatal health in developing countries,” Acta Paediatrica,
and H. I. Maibach, Eds., Springer, New York, NY, USA, 2012. vol. 91, no. 5, pp. 546–554, 2002.
[103] Z. A. Bhutta, G. L. Darmstadt, B. S. Hasan, and R. A. Haws, [120] A. C. Williams and B. W. Barry, “Penetration enhancers,”
“Community-based interventions for improving perinatal Advanced Drug Delivery Reviews, vol. 56, no. 5, pp. 603–618,
and neonatal health outcomes in developing countries: a 2004.
review of the evidence,” Pediatrics, vol. 115, no. 2, supple- [121] B. Kränke, P. Komericki, and W. Aberer, “Olive oil—contact
ment, pp. 519–617, 2005. sensitizer or irritant?” Contact Dermatitis, vol. 36, no. 1, pp.
[104] M. Lodén, “Do moisturizers work?” Journal of Cosmetic 5–10, 1997.
Dermatology, vol. 2, no. 3-4, pp. 141–149, 2003. [122] M. Isaksson and M. Bruze, “Occupational allergic contact
[105] A. P. James, “Bath oils in the management of dry, pruritic dermatitis from olive oil in a masseur,” Journal of the
skin,” Journal of the American Geriatrics Society, vol. 9, pp. American Academy of Dermatology, vol. 41, no. 2, part 2, pp.
18 Dermatology Research and Practice

312–315, 1999. [139] A. LeFevre, S. D. Shillcutt, S. K. Saha et al., “Cost-


[123] G. A. E. Wong and C. M. King, “Occupational allergic effectiveness of skin-barrier-enhancing emollients among
contact dermatitis from olive oil in pizza making,” Contact preterm infants in Bangladesh,” Bulletin of the World Health
Dermatitis, vol. 50, no. 2, pp. 102–103, 2004. Organization, vol. 88, no. 2, pp. 104–112, 2010.
[124] J. D. Williams and B. J. Tate, “Occupational allergic contact [140] M. Bharathi, V. Sundaram, and P. Kumar, “Skin barrier ther-
dermatitis from olive oil,” Contact Dermatitis, vol. 55, no. 4, apy and neonatal mortality in preterm infants,” Pediatrics,
pp. 251–252, 2006. vol. 123, no. 2, pp. e355–e356, 2009.
[125] S. M. Puhvel, R. M. Reisner, and M. Sakamoto, “Analysis [141] D. H. Brandon, K. Coe, D. Hudson-Barr, T. Oliver, and L.
of lipid composition of isolated human sebaceous gland R. Landerman, “Effectiveness of No-Sting skin protectant
homogenates after incubation with cutaneous bacteria. Thin- and Aquaphor on water loss and skin integrity in premature
layer chromatography,” The Journal of Investigative Dermatol- infants,” Journal of Perinatology, vol. 30, no. 6, pp. 414–419,
ogy, vol. 64, no. 6, pp. 406–411, 1975. 2010.
[126] A. Patzelt, J. Lademann, H. Richter et al., “In vivo investiga- [142] M. Brenner and V. J. Hearing, “The protective role of melanin
tions on the penetration of various oils and their influence against UV damage in human skin,” Photochemistry and
on the skinbarrier,” Skin Research and Technology, vol. 18, no. Photobiology, vol. 84, no. 3, pp. 539–549, 2008.
3, pp. 364–369, 2012. [143] M. C. Mack, N. K. Tierney, E. Ruvolo Jr., G. N. Stamatas,
[127] J. C. DiNardo, “Is mineral oil comedogenic?” Journal of K. M. Martin, and N. Kollias, “Development of solar UVR-
Cosmetic Dermatology, vol. 4, no. 1, pp. 2–3, 2005. related pigmentation begins as early as the first summer of
[128] J. F. Nash, S. D. Gettings, W. Diembeck, M. Chudowski, and life,” The Journal of Investigative Dermatology, vol. 130, no. 9,
A. L. Kraus, “A toxicological review of topical exposure to pp. 2335–2338, 2010.
white mineral oils,” Food and Chemical Toxicology, vol. 34, [144] P. Agache, D. Blanc, C. Barrand, and R. Laurent, “Sebum
no. 2, pp. 213–225, 1996. levels during the first year of life,” The British Journal of
[129] G. L. Darmstadt, A. S. M. N. U. Ahmed, S. K. Saha et Dermatology, vol. 103, no. 6, pp. 643–649, 1980.
al., “Infection control practices reduce nosocomial infection [145] L. Vitellaro-Zuccarello, S. Cappelletti, V. Dal Pozzo Rossi, and
and mortality in preterm infants in Bangladesh,” Journal of M. Sari-Gorla, “Stereological analysis of collagen and elastic
Perinatology, vol. 25, no. 5, pp. 331–335, 2005. fibers in the normal human dermis: variability with age, sex,
[130] A. S. M. N. U. Ahmed, S. K. Saha, M. A. Chowdhury and body region,” The Anatomical Record, vol. 238, no. 2, pp.
et al., “Acceptability of massage with skin barrier-enhancing 153–162, 1994.
emollients in young neonates in Bangladesh,” Journal of [146] N. Garcia Bartels, S. Rösler, P. Martus et al., “Effect of baby
Health, Population and Nutrition, vol. 25, no. 2, pp. 236–240, swimming and baby lotion on the skin barrier of infants
2007. aged 3–6 months,” Journal der Deutschen Dermatologischen
[131] W. H. Edwards, J. M. Conner, and R. F. Soll, “The effect of Gesellschaft, vol. 9, no. 12, pp. 1018–1025, 2011.
prophylactic ointment therapy on nosocomial sepsis rates [147] A. J. Lowe, M. L. Tang, S. C. Dharmage et al., “A phase i
and skin integrity in infants with birth weights of 501 to study of daily treatment with a ceramide-dominant triple
1000 g,” Pediatrics, vol. 113, no. 5, pp. 1195–1203, 2004. lipid mixture commencing in neonates,” BMC Dermatology,
[132] J. M. Conner, R. F. Soll, and W. H. Edwards, “Topical oint- vol. 12, no. 1, article 3, 2012.
ment for preventing infection in preterm infants,” Cochrane [148] G. L. Darmstadt, S. K. Saha, A. S. M. N. U. Ahmed et al.,
Database of Systematic Reviews, no. 1, Article ID CD001150, “Effect of topical emollient treatment of preterm neonates in
2004. Bangladesh on invasion of pathogens into the bloodstream,”
[133] M. O. Visscher, “Update on the use of topical agents in Pediatric Research, vol. 61, no. 5, part 1, pp. 588–593, 2007.
neonates,” Newborn and Infant Nursing Reviews, vol. 9, no.
1, pp. 31–47, 2009.
[134] A. Schuchat, C. Lizano, C. V. Broome, B. Swaminathan,
C. Kim, and K. Winn, “Outbreak of neonatal listeriosis
associated with mineral oil,” Pediatric Infectious Disease
Journal, vol. 10, no. 3, pp. 183–189, 1991.
[135] D. K. Brannan and J. C. Dille, “Type of closure prevents
microbial contamination of cosmetics during consumer use,”
Applied and Environmental Microbiology, vol. 56, no. 5, pp.
1476–1479, 1990.
[136] T. Na’was and A. Alkofahi, “Microbial contamination and
preservative efficacy of topical creams,” Journal of Clinical
Pharmacy and Therapeutics, vol. 19, no. 1, pp. 41–46, 1994.
[137] V. E. Becks and N. M. Lorenzoni, “Pseudomonas aeruginosa
outbreak in a neonatal intensive care unit: a possible link
to contaminated hand lotion,” American Journal of Infection
Control, vol. 23, no. 6, pp. 396–398, 1995.
[138] J. R. Campbell, E. Zaccaria, and C. J. Baker, “Systemic
candidiasis in extremely low birth weight infants receiving
topical petrolatum ointment for skin care: a case-control
study,” Pediatrics, vol. 105, no. 5, pp. 1041–1045, 2000.

You might also like